Recurrent driver mutations in FMS-related receptor tyrosine kinase 3 (FLT3) occur in around one-third of patients with de novo acute myeloid leukemia (AML). Although most FLT3 mutations are secondary events in leukemogenesis, they are associated with accelerated clonal expansion and disease progression, and treatment with the tyrosine kinase inhibitor midostaurin has been shown to increase patients’ long-term survival. However, the efficacy of FLT3 inhibitors in eliminating FLT3-mutated clones is variable.
Finding suitable antigens for immunotherapy of myeloid malignancies, particularly acute myeloid leukemia (AML), is an urgent clinical need. Most AML candidate targets, including CD123, are co-expressed by hematopoietic stem and progenitor cells (HSCPs), with the subsequent risk of myelosuppression associated with myeloid cell-targeted chimeric antigen receptor (CAR) T therapy.
The structures of the majority of PD-1/PD-L1 inhibitors currently in use are derived from the arylmethylamine/biphenyl scaffold. Researchers from Southern Medical University reported on the discovery and preclinical evaluation of a novel series of non-arylmethylamine-based PD-1/PD-L1 inhibitors for use in cancer immunotherapy.
Current therapies based on immune checkpoint blockade are effective and offer a valid option for treatment, but many patients develop either primary or acquired resistance to treatment. Previous research has shown that the deletion of protein tyrosine phosphatases PTPN2 and PTPN1 results in an increase in the sensitization of tumor cells and the promotion of antitumor immunity.
The activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is key for antitumor immunity. However, the development of STING agonist-based strategies in cancer has so far encountered limitations such as incomplete tumor regression or adverse effects derived from chronic activation.
A presentation given recently by Medicenna Therapeutics Corp. highlighted preclinical data for the company’s new anti-PD1-IL-2 BiSKIT (Bifunctional SuperKine for ImmunoTherapy) candidate, MDNA-223, being developed as a anticancer therapeutic candidate.
Researchers from MD Anderson Cancer Center recently presented the discovery and preclinical evaluation of LLO-CD47, a novel protein-antibody conjugate linking anti-CD47 to Listeriolysin O (LLO), a pore-forming protein secreted by Listeria monocytogenes to escape lysosomes.
Ocean Biomedical Inc. has demonstrated the effectiveness of its anti-chitinase 3-like-1 (CHI3L1) antibody in suppressing and reversing tumor growth in studies of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) cells.
Sorrento Therapeutics Inc. has divulged antibody-drug conjugates comprising antibodies targeting HER2 covalently linked to exatecan through a linker. They are reported to be useful for the treatment of cancer.
Researchers at Firefly Bio Inc. have prepared antibody-drug conjugates (ADCs) comprising monoclonal antibodies targeting HER2 covalently linked to stimulator of interferon genes protein (STING; TMEM173) agonists through a linker. They are reported to be useful for the treatment of cancer, autoimmune disease, inflammation and infections.
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